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Digestive system
1. Microscopic anatomy of esophagus,
stomach, small and large intestine
2. Microscopic anatomy of pancreas,
liver, overview of GIT embryology
1. Microscopic anatomy of liver and bile ducts
2. Microscopic anatomy of pancreas
3. Embryonic development of digestive system, liver and
pancreas
- Macro – a microscopic anatomy
- Definition and structure of liver lobulus
- Hepatocytes and other liver cells
- Intra- a extrahepatic bile ducts
- Gall bladder
- Pancreatic acini and ducts
- Islets of Langerhans
- Primitive gut derivatives
- Changes in morphology and lovalization druing development
- Regeneration
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LIVER (HEPAR)
• Liver parenchyma – biggest gland in
human body
• C.t. capsule
• Nutritive and functional blood supply
• Endocrine and exocrine function
• Uniform histology of all four major
anatomic lobules and segments:
- Hepatocytes and other cell
types
- C.t. stroma
- Blood and lymphatic vessels
- Sinusoids
- Innervation
- C.t. capsule
- Serosa
CAPSULA FIBROSA HEPATIS
− Serous mesothelium
− C.t. – collagen and elastic fibers
− 70-100µm
− Porta hepatis
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CAPSULA FIBROSA HEPATIS
Porta hepatis
VASCULARISATION
FUNCTION
• capillary stream of stomach and intestine
• vena portae
• interlobular veins
• circumlobular venules
NUTRITIVE
• aorta
• arteria hepatica
• segmental arteries
• interlobular arteries
• circumlobular arteriols
• hepatic sinusoids
• venae centrales hepatis
• venae sublobulares
• venae hepaticae
• vena cava inferior
70% 30% IVC
V. hepatica d. m. s.
Porta hepatis
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VASKULARIZACE
Gartner, Hiatt: Color Textbook of Histology (2001)
MICROSCOPIC SEGMENTATION OF LIVER
• Three possible definitions
• Histological – lobulus venae centralis
• Metabolic – liver acinus
− metabolic zone 1 – 3
− oxygenation of hepatocytes
• Functional (physiological historical) unit
– lobulus venae interlobularis
(portal acinus)
wiki
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Liver acinus
metabolic divergence dependent
on arterio-venous gradients
Zone I (periportal) Zone III (perivenous)
oxidative processes glycogen synthesis
beta-oxidation of fatty acids glycolysis
catabolism of aminoacids lipogenesis
gluconeogenesis ketogenesis
production of urea production of glutamine
synthesis of cholesterol synthesis of bile acids
glycogenolysis biotransformation
production of bile
− Classical morphological unit
− Polygonal cells (hexagonal), 0.7 x 2mm
− Central vein
− Radial cords of hepatocytes
− Liver sinusoids
− Portal triad, portobilliary region
CENTRAL VEIN LOBULUS
Lobulus venae centralis
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LALCENTRAL VEIN LOBULUS
Lobulus venae centralis
Contact of 3-4 neighboring lobuli
• Interlobular artery (a. interlobularis)
• Interlobular vein (v. interlobularis)
• Interlobular bile duct (d. bilifer interlobularis)
• Lymphatic vessels
• Innervation – nervus vagus
Loose interstitial c.t.
CENTRAL VEIN LOBULUS
Portal triad
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Ham: Textbook of Histology
PORTAL TRIAD
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CENTRAL VEIN
LOBULUS VENAE CENTRALIS
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• Hepatocytes arranged to cords, width 1-2
cells, often anastomoses
• Sinusoids
– 9-15µm
– Anastomosing network of flat endothelial
cells
– Basal membrane absent - no diffusion
barrier
– Fenestrations - 100nm, diaphragm absent
– Intercellular space
– Perisinusoidal (Dissé) apace
– Reticular fibers, perisinusoidal fibroblasts
– Dispersed Kupfer cells (monocytemacrophage
system)
– Perisinusoidal cells of Ito
• Vena centralis – thin-walled vessel,
draining blood from sinusoids
LOBULUS VENAE CENTRALIS
Hepatocytes and liver sinusoids
• Space of Disse
– Connection of space of Disse and sinusoidal
lumen by fenestrated endothelium
– Hepatocytes in direct contact with plasma
(microvilli)
– Cells of Ito
LOBULUS VENAE CENTRALIS
Hepatocytes and liver sinusoids
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LIVER SINUSOIDS
INNER SURFACE OF LIVER SINUSOID – SEM
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KUPFFER CELLS
• Liver macrophages
• Mononuclear phagocyte system
• Phagocytosis of particles, damaged
erythrocytes and pathogens
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CELLS OF ITO
• Star-shape (stellate, perisinusoidal) cells
• Lipid droplets
• Deposition of vitamin A
• fine reticular c.t.
• Antigen presenting cells (lipid antigens)
HEPATOCYTES
• Polygonal cells of liver parenchyma
• 20x30µm
• Irregular trabecules between sinusoids
• Usually one central nucleus. Bi- and multinuclear
cells common (20%)
• Nucleoli
• Lysosomes
• Glycogen
• Functional surfaces:
– Bile pole - secretory– membranes of
neighboring hepatocytes form bile capillary
– Blood pole - absorptive - sinusoidal –
microvilli oriented to space of Dissé
– Membranes with intercellular junctions
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HEPATOCYTES
Long mitochondria with flat or tubular cristae
Apparent RER, SER and Golgi
Glycogen, lipid droplets, lysosomes,
peroxisomes
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Erythrocyte
Tight junction
Bile
capillary
Kupfer cells
Cells of Ito
Nucleus
Space of
Dissé
From plasma:
Glucose, aminoacids, bile acids
Blood proteins (serum albumin, fibrinogen, prothrombin, complement, transferrin, etc.)
Space of
Dissé
Bile acids
Bilirubin
Steroids
Drugs
K+
Tight junction
Bile
capillary
Cholestasis
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METABOLIC ACTVITY OF HEPATOCYTES
• Synthesis and metabolism:
− Proteosynthesis – RER + Golgi (plasma proteins – albumins, prothrombin, fibrinogen)
− Metabolisms of lipids – SER, peroxisomes (lipidic conversion of fatty acids and glucose,
lipoprotein synthesis)
− Metabolism of glucose and saccharides - synthesis of glycogen, glycogenolysis and
gluconeogenesis (insulin / glucagon)
METABOLIC ACTIVITY OF HEPATOCYTES
• Detoxication:
SER (steroids, barbiturates, polyaromatic, lipid soluble compounds, etc., endo- and exotoxins)
ROS
• Peribilliary located lysosomes (autophagy, degradation of endocyted molecules)
• Metabolism and deposition of vitamins and trace elements
• Bile production:
Recycling of bile acids (90%), 10% de novo synthesis, conjugation of toxic bilirubin and
glukuronic acid to nontoxic complex bilirubin-glucuronid
SER
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• Enterohepatic circulation
− Resorption in terminal ileum
− Vena portae
− Sinusoids
Hepatocytes
− Bile capillaries
− Intra and extrahepatic ducts
− Duodenum
Blood pole
Bile pole
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INTRAHEPATIC AND EXTRAHEPATIC BILE
DUCTS
Bile capillaries (billiary canaliculli)
- intercellular space between hepatocytes
- 1-2µm
- no true wall, formed by membranes of
hepatocytes
- intercellular junctions
Canals of Herring
- simple squamous epithelium
Interlobular bile ducts
- cholangiocytes
- cubic or low columnar epithelium + c.t.
Lobar bile ducts
- ductus hepaticus dexter et sinister
- high simple columnar epithelium
Ductus hepaticus, ductus cysticus,
ductus choledochus
- mucosa
- fibromuscular layer
INTRAHEPATIC EXTRAHEPATIC
INTRAHEPATIC BILE DUCTS
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http://alexandria.healthlibrary.ca/documents/notes/bom/unit_4/unit%204%202005/L-
39%202008%20%20histology%20of%20the%20pancreas.xml
INTRAHEPATIC BILE DUCTS
INTRAHEPATIC BILE DUCTS
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INTRAHEPATIC BILE DUCTS
TEM/SEM
Central vein
Circulobular
venule
Portal
arteriole
Interlobular
bile ducts
Cannal of
Herring
Bile capillary
HEPATOCYTESCHOLANGIOCYTES
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Mucosa
- lateral folds
- simple columnar epithelium (cholangiocytes)
- mucinous glands in c.t., goblet cells
Fibromuscular layer
- dense network of collagen and elastic fibers
- leiomyocytes
EXTRAHEPATIC BILE DUCTS
d. hepaticus communis + d. cysticus → d. choledochus
papilla duodeni major
m. sphincter ampullae hepatoduodenalis (sphincter of Oddi)
Bile modification
GALL BLADDER (VESICA FELLEA)
- Wall 1-2mm
- Mucous coat
- Muscle layer
- Serosa/adventitia
Mucous coat
- mucosal folds
- 20-50µm simple columnar epithelium with microvilli
- intercellular junctions
- lamina propria mucosae - loose collagen c.t. with mucinous
tuboalveolar glands
- lamina muscularis mucosae absent
Muscular layer (Muscularis propria)
- 3D network of smooth muscle cells,
- elastic fibers
Large layer of subserous c.t. (l. propria serosae)
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Bile concentration
- Bile secretion by liver– ca 0,8-1l daily
- Gall bladder volume 15-60 ml
- Water resorption
GALL BLADDER (VESICA FELLEA)
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GALL BLADDER (VESICA FELLEA)
mucosa
Muscularis propria
serosa
GALL BLADDER (VESICA FELLEA)
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GALL BLADDER (VESICA FELLEA)
PANCREAS
• Compound, serous, tuboalveolar gland
• Exocrine and endocrine character
– pancreatic acinus
– Islets of Langerhans
• Major duct (Wirsungi) opens to Vater papilla
as a common bile and pancreatic duct
• Dense collagen c.t. capsule
• Septs – blood cells, innervation, and
interlobular ducts
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PANCREAS
PANCREATIC ACINUS
• Pyramidal epithelial cells
• Pancreatic digestive enzymes
• intercalated ducts
• Serous acinar cells
– Polarized secretory cells
– Basophilic
– Apex – Golgi and zymogenic granules
– Microvilli
– Intercellular junctions
• Centroacinar cells
– Centrally located nucleus, squamous
character
– Continuous with intercalated ducts
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PANCREATIC ACINUS
PANCREATIC ACINUS
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PANCREATIC ACINUS
• Centroacinar cells
• Intercalated ducts
– simple squamous epithelium + basal membrane
• Intralobular and interlobular ducts
– simple cubic – low columnar epithelium
• Major pancreatic ducts
– D. pancreaticus major – Wirsungi and D. pancreaticus accessorius - Santorini
– bilayered columnar epithelium and dense collagen c.t.
– intramural mucinous tubular glands, goblet cells, EC cells
PANCREATIC DUCTS
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EXOCRINE FUNCTION OF PANCREAS
• ca 1000-2000 ml daily
• alkalic pH (8.8), HCO3
- (intercalated duct epithelium)
• mucin (epithelium of large ducts)
• Hydrolases
– Trypsinogen
– Chymotrypsinogen
– Proelastases
– Carboxypeptidases
– Pancreatic lipase
– Amylases
– …
Hormonal regulation (secretin, cholecystokinin) + parasympatikus
ENDOCRINE FUNCTION OF PANCREAS
Glucagon
Glycogen consumption in tissues and
muscles
Increase of blood glucose
Insulin
Increase of membrane
permeability for glucose
Glucose oxidation in tissues
Decrease of blood glucose
Synthesis of glucan in muscles
and liver
Somatostatin
Inhibition of GIT hormones
Pancreatic polypeptide
Autoregulation of pancreatic
secretion
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ISLETS OF LANGERHANS
• Clusters of pale cells
• ca 1,5 × 106
• Thin c.t. capsule
• Cords of epithelial cells
• Sinusoids
• General characteristics of APUD cells
• A, B, D, PP cells
A cells: 20%, glucagon
B cells: 60-70%, insulin
D cells: minor, somatostatin
PP cells: minor, pancreatic polypeptide
ISLETS OF LANGERHANS
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PRIMITIVE GUT
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4th and 5th week in GIT development
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STOMACH ROTATION
WEEK cca 4th 5th
EMBRYO SIZE 3 mm 5 mm
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INTESTINAL ROTATION
WEEK cca early 8th
EMBRYO SIZE 28 mm
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WEEK cca late 8th
EMBRYO SIZE 35 mm
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DIVERTICULUM MECKELI
OMPHALOCELE
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ABNORMAL INTESTINAL ROTATION
ILEUM DEVELOPMENT AND ABNORMALITIES
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ANUS DEVELOPMENT AND ITS ABNORMALITIES
ANUS DEVELOPMENT AND ITS ABNORMALITIES
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EMBRYONIC DEVELOPMENT OF LIVER
• Differentiation of endoderm and formation primitive gut
• Growth factors of mesoderm determine identity of individual parts
• Interactions with mesoderm of septum transversum and vv. omphalomesentericae
EMBRYONIC DEVELOPMENT OF LIVER
• Diverticulum of embryonic duodenum - liver
diverticulum
• Pars hepatica (parenchyma + ductus hepaticus)
and pars cystica (ductus cysticus + gall bladder)
form d. choledochus
• Rapidly proliferating cells penetrate septum
transversum (mesodermal plate between
pericardial cavity and yolk sac) and growth into
ventral mesentery
• liver cords – parenchyma
• Interactions between cells of liver cords and vv.
omphalomesentericae induce development liver
sinusoids
• C.t. , Kupffer and hematopoieticcells – from
mesoderm of septum transversum
• Surface mesoderm differentiate into visceral
peritoneum
•10th week
- 10% of body volume
- hematopoiesis
• 12th week
- bile production
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EMBRYONIC DEVELOPMENT OF LIVER
EMBRYONIC DEVELOPMENT OF LIVER
In vivo In vitro
Growth and differentiation factors
(FGF, TGF, Wnt atd.)
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REGENERATION OF LIVER TISSUE
- complex physiological response to damage of liver tissue
- induction of proliferation and growth of liver parenchyma
- hepatocyte proliferation
- activation of endogenous progenitor cells
- differentiation of exogenous multipotent cells
- 6th week of development
- two endodermal diverticula
- dorsal and ventral duodenal diverticulum
(= pancreas dorsale et ventrale)
- after rotation of duodenal curve both
diverticula fuse
- ducts persist (ventral - major and dorsal -
accessorius)
- first ductal system develops
- the secretory acini follow
- cells that are not part of ductal structures
differentiate into Islets of Langerhans
- since 4th month in utero - secretory
activity
EMBRYONIC DEVELOPMENT OF PANCREAS
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EMBRYONIC DEVELOPMENT OF PANCREAS
A – hESC → endoderm
B – primitive gut
C – foregut
D – pancreatic precursors
E – Insulin producing β-buňky
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- Microscopic anatomy of liver: endocrine and exocrine function of liver,
vascularization, liver lobulus and its definition, liver cells, ultrastructure and
function of hepatocytes, organization of intra- and extra-hepatic passages
- Microscopic anatomy of pancreas: endocrine and exocrine function,
pancreatic acinus and its ducts, ultrastructure and function of acinar cells,
Islets of Langerhans and their structure, cell types of Islet of Langerhans
and their function
- Embryonic development and morphogenesis of digestive tube, liver and
pancreas, primitive gut and its derivatives, esophagus, stomach, intestine.
Flexion of embryo and rotation, liver and pancreatic diverticulum,
differentiation of individual cell types.
Summary of GIT II
• SEE IS FOR DETAILS
•Sadler: Langman’s Medical Embryology, 2000
• Ovalle&Nahirney: Netter’s Essential Histology, 2008
• Klika&Vacek: Histologie, 1974
• Ross&Pawlina: Histology (a text and atlas), 2011
• Ross&Romrell: Histology (a text and atlas), 1989
• Berman: Color Atlas of Basic Histology
• Ústav histologie & embryologie LF MU, www.med.muni.cz/histology
- LESSONS, LECTURES AND PRACTICALS
• Čech S., Horký D., Sedláčková M.: Přehled embryologie člověka, Brno, LF MU, 2011
• Horký D., Čech S.: Mikroskopická anatomie, Brno, LF MU, 2011
• Lullmann-Rauch R.: Histologie, Grada 2012
• Ehrmann J., Hůlek P., et al. Hepatologie, Grada 2010
Study materials
http://www.stembook.org/
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Thank you for attention
Petr Vaňhara, PhD
Ústav histologie a embryologie LF MU
pvanhara@med.muni.cz
http://www.med.muni.cz/histology
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